Apoptosis (programmed cell death) is activated by diverse stimuli, including many that are characteristic of malignant cells including cell cycle deregulation, aberrant signal transduction and stress associated with an unfavorable microenvironment. Cancer cells also demonstrate defects in apoptotic pathways that allow them to evade programmed cell death and that create inherent resistance to many chemotherapeutic agents. The Inhibitors of Apoptosis Proteins (IAPs) are a family of eight proteins defined by the presence of a protein domain, the BIR domain, initially identified in a Baculoviral protein that inhibited apoptosis. Some IAP family members are clearly involved in suppression of apoptosis. The evidence is strongest for XIAP, CIAP1 and CIAP2 (Hunter Apoptosis; 12:1543-1568, 2007), although the mechanisms through which these proteins influence apoptosis are different. There is strong evidence that XIAP directly binds caspases 3, 7 and 9, and that this binding suppresses apoptosis (Deveraux, et al Nature; 388:300-4, 1997). By contrast, the evidence for the CIAP proteins as direct suppressors of caspase activity is weaker. However, the CIAP1 and CIAP2 proteins are components of death receptor signaling complexes where they influence cell survival or death through the Nuclear Factor kappa B (NF-κB) pathway. Activation of death receptor signaling can induce NF-κB survival signaling or apoptosis, depending on cellular context. In some tumor cells, IAP antagonists induce apoptosis via a mechanism that requires TNF-α and RIPK1 (Gaither Cancer Research; 67: 11493-98, 2007). Therefore, IAPs appear to be attractive targets in cancer.